Title:Angiopoietin-1 and C16 Peptide Attenuate Vascular and Inflammatory Responses in Experimental Allergic Encephalomyelitis
Volume: 15
Issue: 4
Author(s): Beibei Wang, Ke-wei Tian, Fan Zhang, Hong Jiang and Shu Han
Affiliation:
Keywords:
Angiopoietin-1, C16 peptide, combination therapy, experimental autoimmune encephalitis, multiple sclerosis.
Abstract: Breakdown of normal blood-brain barrier function and accompanying vascular leakage are
fundamental stages in the onset of multiple sclerosis and its animal counterpart, experimental allergic
encephalomyelitis. In the present study, angiopoietin-1, an endothelial growth factor well known for
its role in establishing and maintaining vascular integrity, and C16, a peptide that competitively binds
to integrin αvβ3 expressed on endothelial cells, were used to treat acute experimental allergic encephalomyelitis in Lewis
rats. Angiopoietin-1 was more effective than C16 for reducing inflammation-induced vascular leakage. Moreover,
treatment with a combination of angiopoietin-1 and C16 resulted in greater effects, not only in alleviating inflammation
and reducing axonal loss/demyelination but also in down-regulating pro-inflammatory cytokine expression and improving
electrophysiological dysfunction, than treatment with either angiopoietin-1 or C16 alone. Different protective effects were
observed with angiopoietin-1 and C16 treatment suggesting that these proteins target specific receptors to act through
different pathways. Furthermore, angiopoietin-1 and C16 may form the basis of a promising therapeutic strategy for
experimental allergic encephalomyelitis and multiple sclerosis.